There are a variety of conditions in humans which are characterized by a high level of bone resorption and/or by an abnormal balance between bone formation and bone resorption. Among the more common of these are osteoporosis, Paget's disease, and conditions related to the progress of benign and malignant tumors of the bone and metastatic cancers that have migrated to bone cells from elsewhere in the body, e.g., from prostate or breast initial tumors. Other conditions associated with changes in collagen metabolism include osteomalacial diseases, rickets, abnormal growth in children, renal osteodystrophy, and drug-induced osteopenia. Further, abnormalities in bone metabolism are often side effects of thyroid treatment and thyroid conditions per se, such as primary hypothyroidism and thyrotoxicosis as well as Cushing's disease.
It has been recognized that disorders of bone resorption or other conditions characterized by an abnormal balance between bone formation and bone resorption can be detected by altered levels of pyridinium crosslinks in urine and serum (e.g., PCT Pub. Nos. WO 94/14072 (Kung et al.), WO 94/03814 (Cerelli et al.), WO 91/10141 (Robins), WO 91/08478 (Eyre) and WO 89/04491 (Eyre)). The crosslinks take the form of compounds containing a central 3-hydroxy pyridinium ring in which the ring nitrogen is derived from the epsilon amino group of lysine or hydroxylysine, and which occur in collagen as trivalent crosslinking species which crosslink the three polypeptide chains in collagen. In urine and blood, the crosslinks are present as a mixture of pyridinium species consisting of the central pyridinium core (pyridinoline or deoxypyridinoline) with and without additional collagen amino acid residues and/or glycosyl groups still attached.
However, analyses of urine or blood entail certain disadvantages. Assays based on blood generally require samples to be collected by specially trained personnel, increasing the cost of the procedure. Also, blood samples may create the risk of transmitting diseases such as AIDS to those involved with collecting, transporting, and analyzing the samples. Assays based on urine, on the other hand, are often associated with patient discomfort in relation to collecting the sample. In the present invention, these problems are avoided using a method based on collection and analysis of a sweat sample.